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基质血管成分与脂肪间充质干细胞在重塑增生性瘢痕中的比较。

Comparison between Stromal Vascular Fraction and Adipose Mesenchymal Stem Cells in Remodeling Hypertrophic Scars.

作者信息

Domergue Sophie, Bony Claire, Maumus Marie, Toupet Karine, Frouin Eric, Rigau Valérie, Vozenin Marie-Catherine, Magalon Guy, Jorgensen Christian, Noël Danièle

机构信息

Inserm, U1183, Hôpital Saint-Eloi, Montpellier, F-34295, France.

Montpellier University, UFR de Médecine, Montpellier, F-34967, France.

出版信息

PLoS One. 2016 May 26;11(5):e0156161. doi: 10.1371/journal.pone.0156161. eCollection 2016.

Abstract

Hypertrophic scars (HTS) are characterized by excessive amount of collagen deposition and principally occur following burn injuries or surgeries. In absence of effective treatments, the use of mesenchymal stem/stromal cells, which have been shown to attenuate fibrosis in various applications, seems of interest. The objectives of the present study were therefore to evaluate the effect of human adipose tissue-derived mesenchymal stem cells (hASC) on a pre-existing HTS in a humanized skin graft model in Nude mice and to compare the efficacy of hASCs versus stromal vascular fraction (SVF). We found that injection of SVF or hASCs resulted in an attenuation of HTS as noticed after clinical evaluation of skin thickness, which was associated with lower total collagen contents in the skins of treated mice and a reduced dermis thickness after histological analysis. Although both SVF and hASCs were able to significantly reduce the clinical and histological parameters of HTS, hASCs appeared to be more efficient than SVF. The therapeutic effect of hASCs was attributed to higher expression of TGFβ3 and HGF, which are important anti-fibrotic mediators, and to higher levels of MMP-2 and MMP-2/TIMP-2 ratio, which reflect the remodelling activity responsible for fibrosis resorption. These results demonstrated the therapeutic potential of hASCs for clinical applications of hypertrophic scarring.

摘要

肥厚性瘢痕(HTS)的特征是胶原蛋白过度沉积,主要发生在烧伤或手术后。在缺乏有效治疗方法的情况下,使用间充质干/基质细胞似乎很有意义,因为在各种应用中已证明这些细胞可减轻纤维化。因此,本研究的目的是在裸鼠人源化皮肤移植模型中评估人脂肪组织来源的间充质干细胞(hASC)对已存在的HTS的影响,并比较hASC与基质血管成分(SVF)的疗效。我们发现,注射SVF或hASC后,如临床评估皮肤厚度时所观察到的,HTS有所减轻,这与治疗小鼠皮肤中总胶原蛋白含量降低以及组织学分析后真皮厚度减小有关。尽管SVF和hASC都能够显著降低HTS的临床和组织学参数,但hASC似乎比SVF更有效。hASC的治疗效果归因于重要的抗纤维化介质TGFβ3和HGF的高表达,以及反映负责纤维化吸收的重塑活性的MMP-2和MMP-2/TIMP-2比值的高水平。这些结果证明了hASC在肥厚性瘢痕临床应用中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020d/4881943/e622864bc01e/pone.0156161.g001.jpg

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